USPTO Patents Application 10551504

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PATENT COOPERATION TREATY

PCT

INTERNATIONAL PRELIMINARY REPORT ON PATENTABILITY

(Chapter I of the Patent Cooperation Treaty)

(PCT Rule Ubis)

Applicant's 01 agent's file reference

FOR FURTHER ACTION

See item 4 below

C1-A0508P

International application No.

International filing date (da\/monlWyear)

Priority date (dav/montli/vcar)

PCT/JP2006/311600

09 June 2006 (09.06.2006)

10 June 2005 ('l 0.06.2005)

International Patent Classification (8th edition unless older edition indicated)

See relevant information in Form PCT/ISA/237

Applicant

CHUGAI SEIYAKU KABUSHIKI KAISHA

1. This international preliminary report on patentability (Chapter I) is issued by the International Bureau on behalf of the
International Searching Authority under Rule 44 bis. 1 (a).

2. This REPORT consists of a total of 8 sheets, including this cover sheet.

In the attached sheets, any reference to the written opinion of the International Searching Authority should be read as a reference
to the international preliminary report on patentability (Chapter I) instead.

3. This report contains indications relating to the following items:

Box No.

I

Basis of the report

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Box No.

n

Priority

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Box No.

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Non-establishment of opinion with regard to novelty, inventive step and industrial
applicability

Box No.

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Lack of unity of invention

IE)

Box No.

V

Reasoned statement under Article 35(2) with regard to novelty, inventive step or industrial
applicability: citations and explanations supporting such statement

El

Box No.

VI

Certain documents cited

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Box No.

vn

Certain defects in the international application

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Box No.

VIII

Certain observations on the international application

4. The International Bureau will communicate this report to designated Offices in accordance with Rules 44bis3(c) and 93bis.\ but
not. except where the applicant makes an express request under Article 23(2), before the expiration of 30 months from the priority
date (Rule AAbis .2).

Date of issuance of this report

11 December 2007 (11.12.2007)

The International Bureau of WIPO
34. chemin des Colombettes
1211 Geneva 20. Switzerland

Facsimile No. +41 22 338 82 70

Authorized officer

Yoshiko Kuwahara

e-mail: pt07.pct@wipo.int

Form PCT/IB/373 (January 2004)

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PATENT COOPERATION TREATY

From the

INTERNATIONAL SEARCHING AUTHORITY

To:

PCT

'At

WRITTEN OPINION OF THE
INTERNATIONAL SEARCHING AUTHORITY

(PCT Rule Aibis.i)

Date of mailing
(day/month/year)

Applicant's or agent's file reference

C1-A0508P

FOR FURTHER ACTION

See paragraph 2 below

Internati ona] application No.

PCT/JP2006/311600

International filing dale [day/mo rah/year)

09.06.2006

Priority dale (day/nwitfh/year)

10.06.2005

International Patent Classification (IPC) or both national classification and IPC

A61K39/395(2006.01) i, A61K9/19 (2006 . 01) i, A61K47/02 (2006 . 01) i,
A61K47/10 (2006.01)1, A61K47/18 (2006 . 01) i, A61K47/22 (2006 . 01) i,

Applicant

CHUGAI SEIYAKU KABUSHIKI KAISHA

This opinion contains indications relating to the following items:
Basis of the opinion
Priority

Non-establishment of opinion with regard to novelty, inventive step and industrial applicability
Lack of unity of invention

Reasoned statement under Rule 43£H5.1(a)(i) with regard to novelty, inventive step or industrial
applicability: citations and explanations supporting such statement

Certain documents cited

Certain defects in the international application
Certain observations on the international application

FURTHER ACTION

If a demand for international preliminary examination is made, this opinion will be considered to be a written opinion of the
International Preliminary Examining Authority ("IPEA") except that this does not apply where the applicant chooses an Authority other
than this one to be the IFEA and the chosen IPEA has notified the International Bureau under Rule 66. 1 bis(b) that written opinions of
this International Searching Authority will not be so considered.

If this opinion is. as provided above, considered to be a written opinion of the IPEA. the applicant is invited to submit to the IPEA a
written reply together, where appropriate, with amendments, before the expiration of 3 months from the date of mailing of Form
PCT/ISA/220 or before the expiration of 22 months from the priority date, whichever expires later.

For further options, see Form PCT/ISA/220.

For further details, see notes to Form PCT/ISA/220.

Box No

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Box No

II

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Box No

III

Box No

IV

Box No.

V

Box No.

VI

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Box No

VII

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Box No

VIII

Name and mailing address of the ISA/JP

Date of completion of this opinion

Authorized officer

Facsimile No.

Telephone No.

Form PCT/ISA/237 (cover sheet) (April 2005)

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WRITTEN OPINION OF THE
INTERNATIONAL SEARCHING AUTHORITY

International application No.

PCT/JP2006/311600

Box No. I

Basis of this opinion

. which is the language of a

translation furnished for the purposes of international search (Rule 12.3(a) and 23.1(b)).

2. With regard to any nucleotide and/or amino acid sequence disclosed in the international application and necessary to the claimed
invention, this opinion has been established on the basis of:

a. type of material

|^^| a sequence listing

' J table(s( related to the sequence listing

b. format of material
j J on paper

in electronic form

c. time of filing/furnishing

13

contained in the international application as filed

filed together with the international application in electronic form

furnished subsequently to this Authority for the purposes of search

In addition, in the case that more than one version or copy of a sequence listing and/or table(s) relating thereto has been filed or
fumished. the required statements that the information in the subsequent or additional copies is identical to that in the application as
filed or does not go beyond the application as filed, as appropriate, were furnished

4.

Additional comments:

Form PCT/ISA/237 (Box No. I) (April 2005)

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WRITTEN OPINION OF THE
INTERNATIONAL SEARCHING AUTHORITY

Box No. IV

Lack of unity of invention

Inresponse to the invitation (Form PCT/ISA/206) to pay additional fees the applicant has, within the applicable time limit:

□
□
□

not paid additional fees

paid additional fees under protest and, where applicable, the protest fee

paid additional fees under protest but the applicable protest fee was not paid

paid additional fees

* □

This Aulhority found lhat the requirement of unity of invention is not complied with and chose not to invite the applicant to pay
additional fees.

not complied with for the following reasons:

A. The subject matters of claims ( 1 -6. 10, 12-19, 23,24.36-42 (respectively partially), 9 and 22)relateto
a pharmaceutical composition containing salt and sc(Fv)2.

B. The subject matters of claims (.1-6. 10. 12-19, 23, 24 and 36-42 (respectively partially)) relate to a
pharmaceutical composition containing amino sugar and sc(Fv)2.

C. The subject matters of claims (1-6, 10, 12-19. 23, 24 and 36-42 (respectively partially)) relate to a
pharmaceutical composition containing sugar alcohol and sc(Fv)2.

D. The subject matters of claims (1-6. 10, 12-19, 23, 24 and 36-42 (respectively partially)) relate to a
pharmaceutical composition containing an amino acid and sc(Fv)2.

E. The subject matters of claims (1-6. 10, 12-19, 23. 24, 36-42 (respectively partially), 7, 8. 20 and 21)
relate to a pharmaceutical composition containing a pH adjusting agent and sc(Fv)2.

F. The subject matters of claims (12. 36 (partially). 1 1, and 25) relate to a freeze-dried preparation
containing sc(Fv)2.

G. The subject matters of claims (26-35) relate to a method for suppressing isomerization of an active
ingredient in a pharmaceutical composition.

H. The subject matter of claim (43) relates to a method for screening substances which suppress
isomerization of sc(Fv)2.

The pharmaceutical composition containing sc(Fv)2, which is common to A and B-F, is publicly
known, for example, as described in the document ("Treatment of human B cell lymphoma xenografts
with a CD3 x CD19 diabody and T cells," (B. Cochlovius), Journal of immunology, 2000. Vol. 165, No.
2, pages 888 to 895).

The pharmaceutical composition which is a matter common to A and G is publicly known
without mentioning the document.

Therefore, these common matters are not considered to be special technical features, since they
are within the prior art. Moreover, there is no other matter that is common to all the claims and considered
to be any special technical feature.

H is neither a method for producing substances which suppress an isomerization reaction of
sc(Fv)2 such as an amino sugar nor a method for using the substances. Moreover, H does not give any
suggestion regarding a specified structure of compounds required for suppressing isomerization of
sc(Fv)2. Accordingly, there is no single general inventive concept in A and H.

Therefore, the number of inventions included in the application concerned is eight.

4. Consequently, this opinion has been established in respect of the following parts of the international application:

Form PCT/ISA/237 (Box No. IV> (April 2005)

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WRITTEN OPINION OF THE
INTERNATIONAL SEARCHING AUTHORITY

International application No.

PCT/JP2006/311600

Box No. V

Reasoned statement underRule 43bis.l(a)(i) with regard to novelty, inventive step or industrial applicability;

Statement

Novelty <N>

Claims

10, 12, 13. 23. 24 and 36-42 (respectively partially)

YES

Claims

1-6, 1 4-19 ( respectively partially), 9 and 22

NO

Inventive step (IS)

Claims

12, 13, 23, 21 and 36-42 (respectively partially)

YES

Claims

1-6, 10, 14-19 (respectively partially), 9 and 22

NO

Industrial applicability (1A)

Claims

1-6, 10, 12-13, 23, 24, 36-43 (respectively partially),

9 and 22

YES

Claims

NO

Citations and explanations:

Document 1: "Treatment of human B cell lymphoma xenografts with a CD3 x CD 19 diabody and T
cells," (B. Cochlovius), Journal of immunology, 2000, VoL 165, No. 2, pages 888 to 895
Document 2: WO, 2004-019966. Al (Chugai Seiyaku K.K.), 1 1 March, 2003 (11.03.04), & EP,
1541165, Al, & US, 2006-058511. Al

Document 3: JP, 2003-515323, A (Oxford Biomedica (UK) Ltd.). 7 May, 2003 (07.05.03), & WO,
2001-36486, A2, & EP, 1242456, & US, 2003-083290, Al, & US, 2004-131591, Al, & US, 2004-
265275, Al, & US. 2006-014222, Al

Document 4: JP, 2002-543822, A (Smithkline Beecham Corp., US), 24 December, 2002 (24.12.02),
& WO. 2000-69462. Al. & EP, 1178829, Al

(1) The subject matters of claims 1-6, 14-19 (respectively partially) (parts containing salt), 9 and 22
do not appear to be novel or to involve an inventive step, since they are described in document 1
cited in the ISR.

Especially, document 1 describes a pharmaceutical composition where a CD3 x CD 19
diabody (corresponding to sc(Fv)2) is dissolved in PBS (page 889, items "Diabody expression and
purification" and "Pharmacokinetic studies").

(2) The subject matter of claim 10 (partially) (part containing salt) does not appear to involve an
inventive step in view of documents 1-4 cited in the ISR.

Document 1 does not describe that a composition containing sc(Fv)2 and salt is employed as
a freeze-dried preparation.

As described in documents 2-4, however, it is a well-known art to employ a pharmaceutical
composition containing an antibody like scFv, etc., as a freeze-dried preparation.

Therefore, a person skilled in the art could have easily conceived of employing the
pharmaceutical composition described in document 1 containing sc(Fv)2 and salt as a freeze-dried
preparation.

(3) The subject matters of claims 12, 13, 23, 24 and 36-42 (respectively partially)(parts containing
salt) appear to be novel and to involve an inventive step, since they are neither described nor
disclosed in any of the documents cited in the ISR.

The isomerization reactions of bivalent scFv and single chain diabody, and the method for
suppressing the isomerization reactions described in claims 12, 13, 23, 24 and 36-42 (respectively
partially) (parts containing salt), are neither described in any of the documents cited in the ISR or the
documents related to the present invention, nor obvious to a person skilled in the art.

Form PCT/ISA/237 (Box No. V) (April 2005)

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WRITTEN OPINION OF THE
INTERNATIONAL SEARCHING AUTHORITY

International application No.

PCT/ JP2006/311600

Box No. V Reasoned statement under Rule 43bis.l(a)(i) with regard to novelty, Inventive step or industrial applicability;

citations and explanations supporting such statement

Form PCT/ISA/237 (Box No. V) (April 2005)

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WRITTEN OPINION OF THE
INTERNATIONAL SEARCHING AUTHORITY

International application No.

PCT/JP2006/311600

Box No. VI

Certain documents cited

1. Certain published documents (Rule 43bis.l and 70.10)

Application No. Publication dale Filing date Priority dale (valid claim)
Patent No. (day/month/year) (day/motith/year) (day/moifiWyear)

wo 2005/107784 ai [P, x] 17.11.2005 11.05.2005 11.05.2004

2. Non-written disclosures (Rule 43iw's.I and 70.9)

Date of written disclosure

Kind of non- written disclosure Date of non- written disclosure referring to non- written disclosure

(Aay/monih/year) (day/monXb/\>ear)

Form PCT/ISA/237 (Box No. VI) (April 2005)

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WRITTEN OPINION OF THE
INTERNATIONAL SEARCHING AUTHORITY

International application No.

PCT/JP2006/311600

Supplemental Box

In case the space in any of the preceding boxes is not sufficient.
Continuation of: I nt . CI .

A61K47/2 6 (2006 . 01) i, A61K4 7/46(2006.01)i,
A61P43/00 (200 6. 01) i, G01N3 3/15 (200 6.01) i,
G01N33/50 (2006. 01) i

Form PCT71SA/237 (Supplemental Box) (April 2005)